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Influence of ABCC 2, CYP 2C8 , and CYP 2J2 Polymorphisms on Tacrolimus and Mycophenolate Sodium–Based Treatment in Brazilian Kidney Transplant Recipients
Author(s) -
Genvigir Fabiana D. V.,
Nishikawa Alvaro M.,
Felipe Claudia R.,
TedescoSilva Helio,
Oliveira Nagilla,
Salazar Antony B. C.,
MedinaPestana Jose O.,
Doi Sonia Q.,
Hirata Mario H.,
Hirata Rosario D. C.
Publication year - 2017
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/phar.1928
Subject(s) - tacrolimus , chemistry , pharmacology , single nucleotide polymorphism , mycophenolic acid , mycophenolate , medicine , transplantation , genotype , biochemistry , gene
Study Objective To investigate the influence of single nucleotide polymorphisms ( SNP s) in genes encoding metabolizing enzymes ( CYP 2C8 , CYP 2J2 , and UGT 2B7 ) and transporters ( ABCC 2 and ABCG 2 ) on dose and dose‐adjusted trough blood concentrations (C:D ratio), clinical outcomes, and occurrence of adverse events of tacrolimus and mycophenolate sodium in Brazilian kidney transplant recipients. Design Pharmacogenetic analysis of patients enrolled in a previously published study. Patients One hundred forty‐eight adult kidney transplant recipients treated with tacrolimus, enteric‐coated mycophenolate sodium, and prednisone for 90 days posttransplantation. Measurements and Main Results ABCC 2 c.−24C>T and c.3972C>T, ABCG 2 c.421C>A, CYP 2C8*3 , CYP 2J2 c.−76G>T, and UGT 2B7 c.372A>G SNP s were determined by real‐time polymerase chain reaction. The CYP 3A5*3C SNP data were used to eliminate the confounding effect of this variant on the results. ABCC 2 c.3972T allele carriers showed higher tacrolimus C:D values than did carriers of the c.3972 CC genotype. The CYP 2C8*3 variant was also associated with slightly higher tacrolimus C:D values and higher estimated glomerular filtration rate but only in CYP 3A5‐nonexpressing patients ( CYP 3A5*3C/*3C carriers). None of the SNPs were associated with mycophenolate sodium dose or episodes of biopsy‐confirmed acute rejection or delayed graft function. The CYP 2J2 c.−76T allele was associated with increased risk for treatment‐induced nausea and/or vomiting (OR: 5.30, 95% confidence interval 1.49‐18.79, p<0.05). Conclusion The ABCC 2 c.3972C >T polymorphism affected tacrolimus C:D in Brazilian kidney transplant recipients. Further, CYP 2C8*3 and CYP 2J2 c.−76G>T SNP s influenced the renal function of these patients and the occurrence of adverse events during treatment with tacrolimus and mycophenolate sodium.